A new analytical assay was developed, using gas liquid chromatography with nitrogen phosphorus detection, for the cholinergic agonist arecoline (1, 2, 5, 6-tetrahydro-1-methyl-3-pyridinecarboxylic acid methyl ester). The assay was applied to plasma and tissue samples of animals and to plasma samples of humans. A model was developed for interpretation of the role of drug binding to plasma proteins in determining brain uptake of highly-bound drugs. The model took into account cerebral blood flow and the kinetics of protein binding. A critical review of the issues of pharmacokinetics and pharmacodynamics of centrally acting as they pertain to the elderly was published.